Article

AMP-activated protein kinase is essential for survival in chronic hypoxia.

Dana-Farber Cancer Institute, Department of Medical Oncology, Harvard Medical School, Mayer Building 440, 44 Binney Street, Boston, MA 02115, USA.
Biochemical and Biophysical Research Communications (Impact Factor: 2.28). 06/2008; 370(2):230-4. DOI: 10.1016/j.bbrc.2008.03.056
Source: PubMed

ABSTRACT This study was undertaken to interrogate cancer cell survival during long-term hypoxic stress. Two systems with relevance to carcinogenesis were employed: Fully transformed BJ cells and a renal carcinoma cell line (786-0). The dynamic of AMPK activity was consistent with a prosurvival role during chronic hypoxia. This was further supported by the effects of AMPK agonists and antagonists (AICAR and compound C). Expression of a dominant-negative AMPK alpha resulted in a decreased ATP level and significantly compromised survival in hypoxia. Dose-dependent prosurvival effects of rapamycin were consistent with mTOR inhibition being a critical downstream mediator of AMPK in persistent low oxygen.

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